Limits...
Transpositional shuffling and quality control in male germ cells to enhance evolution of complex organisms.

Werner A, Piatek MJ, Mattick JS - Ann. N. Y. Acad. Sci. (2014)

Bottom Line: This reduces the ability of such organisms to explore evolutionary space, and, consequently, strategies that mitigate this problem likely have a strategic advantage.Cells that fail the genomic quality test are excluded from further development, eventually resulting in a positively selected mature sperm population.We suggest that these processes, enhanced variability and stringent molecular quality control, compensate for the apparent reduced potential of complex animals to adapt and evolve.

View Article: PubMed Central - PubMed

Affiliation: RNA Biology Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle, United Kingdom.

Show MeSH
Schematic representation of the proposed endo-siRNA–based control mechanism. The left side (1–5) shows the mechanism applied to a nonmutagenized gene; the right side represents a gene that has been damaged by a transposon insertion. During the first step, the genes are transcribed in both directions (1 and i) generating fully processed complementary RNA. The sense/antisense mRNAs can either hybridize and become processed into endo-siRNAs (2 and ii) or exported and stored in the chromatoid body (3 and iii). The gene with the transposon insertion, however, produces little, unstable, or incorrectly spliced or folded sense mRNA (represented as a thin line) that fails to reach the chromatoid body (iii). The endo-siRNAs reach the cytoplasm, where both strands are incorporated into a complex with an Argonaute protein (RISC) (4 and iv). RISCs search for and bind to their complementary targets, which are sequestered in significant numbers in the chromatoid bodies (5 and v). If a RISC complex fails to hybridize to a target in the chromatoid body, it will remain mobile and eventually find its target in primary RNAs at the transcribed locus (vi). We propose that the nuclear RISC eventually interferes with the further maturation of the sperm, thus eliminating cells with deleterious TE insertions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390386&req=5

Figure 2: Schematic representation of the proposed endo-siRNA–based control mechanism. The left side (1–5) shows the mechanism applied to a nonmutagenized gene; the right side represents a gene that has been damaged by a transposon insertion. During the first step, the genes are transcribed in both directions (1 and i) generating fully processed complementary RNA. The sense/antisense mRNAs can either hybridize and become processed into endo-siRNAs (2 and ii) or exported and stored in the chromatoid body (3 and iii). The gene with the transposon insertion, however, produces little, unstable, or incorrectly spliced or folded sense mRNA (represented as a thin line) that fails to reach the chromatoid body (iii). The endo-siRNAs reach the cytoplasm, where both strands are incorporated into a complex with an Argonaute protein (RISC) (4 and iv). RISCs search for and bind to their complementary targets, which are sequestered in significant numbers in the chromatoid bodies (5 and v). If a RISC complex fails to hybridize to a target in the chromatoid body, it will remain mobile and eventually find its target in primary RNAs at the transcribed locus (vi). We propose that the nuclear RISC eventually interferes with the further maturation of the sperm, thus eliminating cells with deleterious TE insertions.

Mentions: The scenario that mutational variation and initial selection and quality control have been transferred in substantial part from the zygote to the sperm fits with the known temporal events in spermatogenesis, including DNA demethylation, the activation of transposition, its subsequent suppression by Piwi-interacting RNA (piRNA)–mediated pathways, the genome-wide wave of transcription that is followed by chromatin compaction, and large-scale apoptosis of immature sperm cells.2–4 We propose that these processes represent stages of a developmental program to enable the mobilization of transposable elements (TEs), which, through quasi-random insertion, promote variation in the genome. The transcriptional burst in the meiotic phase of spermatogenesis that produces the most complex transcriptome of all tissue, including the brain,5 represents the next important event in the proposed developmental program. Accordingly, the germ line–specific program6 enables pervasive transcription as the prerequisite for genomic quality screening to reduce the deleterious side effects of transposon insertions and recombination errors (Figs. 1 and 2). Intriguingly, the proposed stringent quality-control mechanism also helps to explain how complex organisms, humans in particular, can thrive in a highly mutagenic environment.7


Transpositional shuffling and quality control in male germ cells to enhance evolution of complex organisms.

Werner A, Piatek MJ, Mattick JS - Ann. N. Y. Acad. Sci. (2014)

Schematic representation of the proposed endo-siRNA–based control mechanism. The left side (1–5) shows the mechanism applied to a nonmutagenized gene; the right side represents a gene that has been damaged by a transposon insertion. During the first step, the genes are transcribed in both directions (1 and i) generating fully processed complementary RNA. The sense/antisense mRNAs can either hybridize and become processed into endo-siRNAs (2 and ii) or exported and stored in the chromatoid body (3 and iii). The gene with the transposon insertion, however, produces little, unstable, or incorrectly spliced or folded sense mRNA (represented as a thin line) that fails to reach the chromatoid body (iii). The endo-siRNAs reach the cytoplasm, where both strands are incorporated into a complex with an Argonaute protein (RISC) (4 and iv). RISCs search for and bind to their complementary targets, which are sequestered in significant numbers in the chromatoid bodies (5 and v). If a RISC complex fails to hybridize to a target in the chromatoid body, it will remain mobile and eventually find its target in primary RNAs at the transcribed locus (vi). We propose that the nuclear RISC eventually interferes with the further maturation of the sperm, thus eliminating cells with deleterious TE insertions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390386&req=5

Figure 2: Schematic representation of the proposed endo-siRNA–based control mechanism. The left side (1–5) shows the mechanism applied to a nonmutagenized gene; the right side represents a gene that has been damaged by a transposon insertion. During the first step, the genes are transcribed in both directions (1 and i) generating fully processed complementary RNA. The sense/antisense mRNAs can either hybridize and become processed into endo-siRNAs (2 and ii) or exported and stored in the chromatoid body (3 and iii). The gene with the transposon insertion, however, produces little, unstable, or incorrectly spliced or folded sense mRNA (represented as a thin line) that fails to reach the chromatoid body (iii). The endo-siRNAs reach the cytoplasm, where both strands are incorporated into a complex with an Argonaute protein (RISC) (4 and iv). RISCs search for and bind to their complementary targets, which are sequestered in significant numbers in the chromatoid bodies (5 and v). If a RISC complex fails to hybridize to a target in the chromatoid body, it will remain mobile and eventually find its target in primary RNAs at the transcribed locus (vi). We propose that the nuclear RISC eventually interferes with the further maturation of the sperm, thus eliminating cells with deleterious TE insertions.
Mentions: The scenario that mutational variation and initial selection and quality control have been transferred in substantial part from the zygote to the sperm fits with the known temporal events in spermatogenesis, including DNA demethylation, the activation of transposition, its subsequent suppression by Piwi-interacting RNA (piRNA)–mediated pathways, the genome-wide wave of transcription that is followed by chromatin compaction, and large-scale apoptosis of immature sperm cells.2–4 We propose that these processes represent stages of a developmental program to enable the mobilization of transposable elements (TEs), which, through quasi-random insertion, promote variation in the genome. The transcriptional burst in the meiotic phase of spermatogenesis that produces the most complex transcriptome of all tissue, including the brain,5 represents the next important event in the proposed developmental program. Accordingly, the germ line–specific program6 enables pervasive transcription as the prerequisite for genomic quality screening to reduce the deleterious side effects of transposon insertions and recombination errors (Figs. 1 and 2). Intriguingly, the proposed stringent quality-control mechanism also helps to explain how complex organisms, humans in particular, can thrive in a highly mutagenic environment.7

Bottom Line: This reduces the ability of such organisms to explore evolutionary space, and, consequently, strategies that mitigate this problem likely have a strategic advantage.Cells that fail the genomic quality test are excluded from further development, eventually resulting in a positively selected mature sperm population.We suggest that these processes, enhanced variability and stringent molecular quality control, compensate for the apparent reduced potential of complex animals to adapt and evolve.

View Article: PubMed Central - PubMed

Affiliation: RNA Biology Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle, United Kingdom.

Show MeSH